Tissue lubrication is crucial for the normal function of articulating joints, eyes, and lungs. Compromised lubrication is a hallmark of disease in these organ systems, warranting investigation into therapeutic strategies to restore function. Current clinical strategies using injections or eye drops to deliver lubricating biopolymers such as hyaluronic acid (HA) to the diseased tissue are largely ineffective because the lubricant is quickly cleared.
Lubrication is key to a number of industrial technologies, including car engines, wind turbines, and hard drives, where chemists work together with engineers to design surfaces that work together with liquid lubricants to achieve low-friction systems. Lubrication in tissues is also important to maintain a low-friction movement within a number of biological systems, including the pleural cavity, the surface of the eye, and diarthroidal joints. Medical devices employed in these tissues generally lack lubrication, hampering their tissue replacement function. In diarthroidal joints, healthy painless movement is facilitated by both molecules at the tissue surface and in the lubricating synovial fluid. Synovial fluid bathes the joint surface with several molecules that contribute to boundary lubrication, including lubricin, surface-active phospholipids, and hyaluronic acid (HA). The role of each of these components has been supported and challenged on the basis of various in vitro studies on cartilage lubrication, however in a healthy joint these molecules work together synergistically to reduce friction coefficients in boundary lubrication to achieve normal physiological performance. Today, therapeutic options to enhance tissue lubrication focus only on replacing or enhancing the lubricant in the fluid phase.
The breakdown of joint lubrication is a major hallmark of osteoarthritis (OA), stimulating significant interest in understanding and enhancing joint lubrication to improve overall joint health. Only about 10% of the cartilage surface area comes into direct contact with the opposite surface during walking in the healthy knee, suggesting the role of boundary lubrication is relatively small. Osteoarthritic knees are further challenged by narrow intra-articular spaces, roughened cartilage surfaces, and often abnormal joint motion. All of these contribute to a much greater reliance on boundary lubrication at the same time that many boundary lubricants are depleted and disrupted by inflammatory processes. The resultant higher friction leads to pain, accelerated degeneration of cartilage, and disease progression. HA is believed to improve joint lubrication through its viscoelastic properties at high molecular weights, although biological functions may also play a role. As a result, one common clinical treatment for OA is injection of HA directly into the joint to improve synovial lubrication. Despite the physical and biological attributes of HA, clinical results of HA injections have been inconclusive and suspect due to the clearly observable rapid turnover of HA molecules within the joint after injection and limited ability to target areas where increased lubrication is needed. Alternative approaches to improving joint health and lubrication are investigating the other synovial fluid components, lubricin and surface active phospholipids. Despite the drastic degenerative changes in the tissue surface with OA and the critical role the surface plays in lubrication, there has been no attempt to target the cartilage surface to improve joint lubrication and overall joint health. In fact, the tissue surface is an ideal focus for therapeutic intervention as it is more stable than the constantly circulating synovial fluid and may be better suited to protect the underlying tissue from exposure to physical and biological elements. Hence, the duration of an enhancement/repair/treatment achieved with hydrogel compositions is limited in time, and frequently requires the recipient to undergo additional and expensive repeat injections/treatments to maintain a desired effect.
A need continues to exist in the tissue repair and reconstructive arts for improved HA containing biomaterial compositions which improve retention of HA in the hydrogel and are longer lasting.